An Open Label, Exploratory Study to Establish the Efficacy and Safety of 1 Year Canakinumab Treatment in Behçet's Disease Patients With Neurologic or Vascular Involvement
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Number of Participants With Attacks
研究概览
简要总结
Primary objective of the study was to evaluate the safety and efficacy of canakinumab on the clinical and inflammatory findings of Behced Disease patients with neurologic and vascular involvement.
详细描述
Primary endpoint: Resolution of acute exacerbation findings related to Behçet's Disease (BD) based on achievements in any of the following items without deterioration on day 30:
For patients with parenchymal neurologic disease: Resolution of acute exacerbation of parenchymal neurologic findings based on improvements in any of the following items without deterioration on Day 30:
- Improvement of muscle strength, ataxia, or other relevant neurologic findings depending on the involved region on neurological examination (by Neuro-Behçet's Disease Score, Modified Expanded Disability Status Scale, and Modified Rankin Scores) cerebrospinal fluid
- Improvement in systemic inflammatory findings (CRP, Erythrocyte Sedimentation Rate , SAA)
- Any decrease in the size of the MRI lesion, or disappearance of contrast enhancement
- Improvement in patients' and physicians global assessment using a 10-cm visual analogue scale (VAS)
Complete response was defined as full clinical recovery to the pre-attack state, disappearance of MRI lesion(s), and normalisation of Cerebrospinal Fluid findings.
Partial response was defined as partial improvement in clinical findings, but with findings still worse than the pre-attack state, and MRI lesions, which become smaller with no or less enhancement, and a decrease in cerebrospinal fluid cell count.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged over 18-60 Behced Disease fulfilling the International Study Group (ISG) criteria, who have a recent exacerbation of large-vessel vascular disease and/or parenchymal neurologic disease For Neurologic Involvement
- •Patients experiencing an acute exacerbation of parenchymal neurologic disease involving brainstem and/or diencephalic region.
- •Exacerbation is defined based on the presence of both of the following:
- •An acute/subacute neurological syndrome including any of hemiparesis, ataxia, dysarthria,headache within the first month of onset of neurologic manifestations (without any prior high dose steroid treatment)
- •Compatible cranial MRI lesion involving brainstem and/or diencephalic region
- •For Vascular Disease :
- •Patients experiencing an acute exacerbation of vascular disease within the last month, involving
- •Large arteries (abdominal aorta, pulmonary arteries, extremity arteries)
- •Large veins (deep vein thrombosis of extremities, caval vein thrombosis, dural sinus thrombosis)
- •Compatible radiological findings (spiral CT, MR, or Doppler ultrasonography)
排除标准
- •For Neurologic Involvement :
- •Presence of severe neurological sequelae from any previous attacks rendering the patient dependent on others physically or mentally
- •Any other neurological cause underlying the picture including ischemic central nervous system lesion on MRI
- •Any previous treatment with biological agents other than interferon-alpha or any previous treatment with cyclophosphamide
- •No interferon in the last 6 months, no Intra Venous Metilprednizolon in the past month
- •For Vascular disease and general :
- •Presence of severe vascular sequelae from any previous attacks rendering the patient dependent on others
- •Any other vascular disease complication the evaluation of exacerbation
- •Any previous treatment with biological agents other than interferon alpha, or any previous treatment with cyclophosphamide
- •No interferon alpha in the last 6 months, no IVMP in the past month
- •History of Squamo Cell Carcinoma OR Basal Cell Carcinoma in previous 5 years. General
- •Presence or history of any other inflammatory rheumatic disease
- •Positive Purified Protein Derivative test (according to local guidance) where an active Tuberculosis infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed) Pregnancy or lactation
- •Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
- •History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin
- •Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding
- •With known sensitivity to canakinumab
- •Use of any other investigational agent in the last 30 days
研究组 & 干预措施
Canakinumab
Canakinumab was administered monthly
干预措施: Canakinumab (Drug)
结局指标
主要结局
Number of Participants With Attacks
时间窗: 30 days
Resolution of acute exacerbation findings related to Behçet's Disease (BD). The attacks were assessed by pyhsician global assesment. For patients with parenchymal neurologic disease: Resolution of acute exacerbation of parenchymal neurologic findings based on improvements in any of the following items without deterioration on Day 30 This was an exploratory trial that was not powered for a statistical analysis.
Modified Expanded Disability Status Scale (EDSS)
时间窗: 30 days
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. Scale range is between 0-10 with 10 being most disability. Mean score of 3 participants who were evaluated in Neurology clinic. Other 5 participants were not evaluated for EDSS.
Visual Analogue Scores (VAS) for Stomachache
时间窗: 30 days
Stomacheache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. VAS is determined separately by physician and the participants.
Ataxia
时间窗: 30 days
Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.
Physician's Global Assessment
时间窗: 30 days
Physician's General Assessments is VAS scale, ranging between 0-5, showing the disease status of participants. Score 0 is the worst outcome; 5 is the best outcome
BDCAF (Behçet's Disease Current Activity Form)
时间窗: 30 days
BDCAF is an assessment that is made by physician for evaluating the disease activity in last four weeks. Score range is 0 to 12, 0 is the best outcome, 12 is the worst outcome.
Neuro-Behçet's Disability Score (NBDS)
时间窗: 30 days
Neuro-Behçet's disability score (NBDS) has been proposed for parenchymal-NBD patients to quantify disabilities. This comprises scores for motor and cognitive status. NBDS is the arithmetic sum of both scores and ranges from 0 to 8, with 8 being death due to NBD. 3 neurologic participants were evaluated.
Erythrocyte Sedimentation Rate (ESR)
时间窗: 30 days
Mean erythrocyte sedimentation rate (ESR) value (8 participants)
SAA (Serum Amyloid A)
时间窗: 30 days
Mean Serum Amyloid A value (8 participants)
Visual Analogue Scores (VAS) for Extremity Assessments
时间窗: 30 days
Extremity assessments were measured by VAS where score 0 means "no pain," and score 10 means "the worst possible pain''. The physicians and participants evaluated VAS separately.
Modified Ranking Score (mRS)
时间窗: 30 days
Mean Modified Rankin Scale (mRS): mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Scores range from 0-5 with 5 being the worst outcome. Only 3 participants from neurology clinic were evaluated with this scale.
Hemoptysis
时间窗: 30 days
The number of the participants with hemoptysis
Visual Analogue Scores (VAS) for Headache
时间窗: 30 days
Headache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. Physician and participant determined the VAS score separately.
Steroid Dose Regimen
时间窗: 30 days
Mean steroid treatment dose (8 participants)
Physical Examination Scores Indicating Change in Muscle Strength
时间窗: 30 days
All 4 extremties were evaluated for muscle strength (upper right, upper left, lower right and lower left) fro each patient. Score 0 is the worst outcome whereas 5 is the best outcome for muscle strength. 3 participants from neurology clinic were assessed.
C-reactive Protein (CRP) Values
时间窗: 30 days
Mean CRP (C-reactive protein) value (8 participants)
Visual Analogue Scores (VAS) for Patients' General Assessments
时间窗: 30 days
Participants assessed their own well-being with VAS (visual analogue scale). Score 0 means the best outcome, score 10 is the worst outcome.
Extremity (Localized) Pain Assessment (VAS)
时间窗: 30 days
Localized pain in the extremities were assessed by visual analogue scale scores ranging between Scale; 0 is the best outcome; 10 is worst.
次要结局
未报告次要终点